Clostridium difficile, commonly referred to as C. diff., is a bacterium best known for causing antibiotic-associated diarrhea. The bacterium is known to cause infection when competing bacteria in the gut have been wiped out following the use of antibiotic treatment. Some people infected with C. diff. are asymptomatic, while others infected may experience severe diarrhea, abdominal pain, fever and a distinctive foul stool odor. C. diff. infections are the most common cause of pseudomembranous colitis and in rare cases can progress to a life-threatening condition such as toxic megacolon. To date, C. diff. is the most prevalent cause of infectious diarrhea and colitis in the United States.
C. diff. was first described in 1935 as Bacillus difficilis following the analysis of fecal samples of healthy newborn infants, in a study conducted by Hall and O'Toole. The species name “difficile” remained due to the difficulty involved in the isolation and study of these bacteria. C. diff was later described as an obligate anaerobic, spore-producing, gram-positive rod, belonging to an ancient group of bacteria called the Clostridia, giving the name Clostridium difficile. Clostridia are motile bacteria that are especially prevalent in soil, but a commensal bacterium of the human intestine. In 1977, Bartlett identified it as an anaerobic bacterium, potent human pathogen and the etiologic agent responsible for antibiotic associated pseudomembranous colitis and recognized it as the major cause of antibiotic-associated diarrhea. C. diff. has since been recognized as a hospital-acquired infection (HAI) pathogen, inflicting morbidity in infected individuals triggered by the widespread use of the antibiotic clindamycin. Over the following years, the antibiotics in the penicillin and cephalosporin families contributed to the C. diff. epidemic.
C. difficile spores can live outside the body for long periods of time, and can be easily spread from patient to patient in healthcare facilities. Therefore, hospital patients, nursing home residents and individuals taking antibiotics are at higher risk for Clostridium difficile infection (CDI) due to the increased chance of exposure. The transfer of C. diff. occurs via fecal-oral route where the spores pass through the stomach and ultimately end up in the colon. Once antibiotics are introduced, the normal enteric flora is suppressed making an environment in which C. diff can proliferate and produce Clostridium difficile-associated diarrhea (CDAD) through toxins A (enterotoxin) and B (cytotoxin). In terms of C. diff., approximately 3% of healthy adult stools test positive where the frequency of stool carriage increases to 16-35% in hospital patients.
When CDI is suspected, a test varies from institution to institution-stool culture, cytotoxin assay, PCR, ELISA, Latex agglutination assay for glutamate dehydrogenase or endoscopy are performed. The most common test used to diagnose C. diff. is ELISA to detect toxin A and B. Once CDI is diagnosed, treatment is administered. The top three medications prescribed are metronidazole, vancomycin, and fidaxomicin. First-line therapy, for mild to moderate C. difficile diarrhea, is restricted to metronidazole. Second-line therapy for severe infections and/or treatment failure is vancomycin. Intravenously-administered vancomycin should not be used for the treatment of C. difficile due to its inability to penetrate the colon and reach therapeutic concentrations via this route of administration. However, orally-administered vancomycin reaches very high concentrations in the colon (generally 500-1000 μg/mL) and cannot be absorbed; thus, oral vancomycin is a favorable choice for the treatment of C. difficile pseudomembranous colitis and Staphylococcal enterocolitis by being confined to the site of infection, and is then excreted fecally.